Genome-wide miRNA profiling of mantle cell lymphoma reveals a distinct subgroup with poor prognosis

Javeed Iqbal, Yulei Shen, Yanyan Liu, Kai Fu, Elaine S. Jaffe, Cuiling Liu, Zhongfeng Liu, Cynthia M. Lachel, Karen Deffenbacher, Timothy C. Greiner, Julie M. Vose, Sharathkumar Bhagavathi, Louis M. Staudt, Lisa Rimsza, Andreas Rosenwald, German Ott, Jan Delabie, Elias Campo, Rita M. Braziel, James R. CookRaymond R. Tubbs, Randy D. Gascoyne, James O. Armitage, Dennis D. Weisenburger, Timothy W. McKeithan, Wing C. Chan

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

miRNA deregulation has been implicated in the pathogenesis of mantle cell lymphoma (MCL). Using a high-throughput quantitative real-time PCR platform, we performed miRNA profiling on cyclin D1-positive MCL (n = 30) and cyclin D1-negative MCL (n = 7) and compared them with small lymphocytic leukemia/ lymphoma (n = 12), aggressive B-cell lymphomas (n = 138), normal B-cell subsets, and stromal cells. We identified a 19-miRNA classifier that included 6 up-regulated miRNAs and 13 down regulated miRNA that was able to distinguish MCL from other aggressive lymphomas. Some of the up-regulated miRNAs are highly expressed in naive B cells. This miRNAclassifier showed consistent results in formalinfixed paraffin-embedded tissues and was able to distinguish cyclin D1-negative MCL from other lymphomas. A 26-miRNA classifier could distinguish MCL from small lymphocytic leukemia/lymphoma, dominated by 23 up-regulated miRNAs in MCL. Unsupervised hierarchical clustering of MCL patients demonstrated a cluster characterized by high expression of miRNAs from the polycistronic miR17-92 cluster and its paralogs, miR-106a-363 and miR-106b-25, and associated with high proliferation gene signature. The other clusters showed enrichment of stroma-associated miRNAs, and also had higher expression of stroma-associated genes. Our clinical outcome analysis in the present study suggested that miRNAs can serve as prognosticators.

Original languageEnglish (US)
Pages (from-to)4939-4948
Number of pages10
JournalBlood
Volume119
Issue number21
DOIs
StatePublished - May 24 2012

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Iqbal, J., Shen, Y., Liu, Y., Fu, K., Jaffe, E. S., Liu, C., Liu, Z., Lachel, C. M., Deffenbacher, K., Greiner, T. C., Vose, J. M., Bhagavathi, S., Staudt, L. M., Rimsza, L., Rosenwald, A., Ott, G., Delabie, J., Campo, E., Braziel, R. M., ... Chan, W. C. (2012). Genome-wide miRNA profiling of mantle cell lymphoma reveals a distinct subgroup with poor prognosis. Blood, 119(21), 4939-4948. https://doi.org/10.1182/blood-2011-07-370122